Spontaneous Fusion with macrophages gives new powers to cancer cells

As we have learned more about the biology of cancer, it has become obvious that, aside from changes to the cancer genome, there are many other factors that determine tumor outcomes. Epigenetics, influences from the microenvironment, exosomes, and interplay with the immune system are now all recognized major players in cancer progression. Fresh evidence from Alain Silk, Melissa Wong, and colleagues at Oregon Health & Science University (OHSU) in Portland implicates a century-old observation—fusion of cancer cells with macrophages—as a new potentiator of cancer progression.

Fresh evidence from researchers at Oregon
Health & Science University implicates
a century-old observation— fusion of cancer
cells with macrophages—as a new potentiator
of cancer progression. They found that
fusion-derived cancer cells exhibited enhanced
adhesive strength, formed tumors more rapidly
than unfused cancer cells, and flourished
under conditions that dramatically
inhibited growth of unfused cells.As we have learned more about the biology of cancer, it has become obvious that, aside from changes to the cancer genome, there are many other factors that determine tumor outcomes. Epigenetics, influences from the microenvironment, exosomes, and interplay with the immune system are now all recognized major players in cancer progression. Fresh evidence from Alain Silk, Melissa Wong, and colleagues at Oregon Health & Science University (OHSU) in Portland implicates a century-old observation—fusion of cancer cells with macrophages—as a new potentiator of cancer progression.

The researchers followed the work of German pathologist Otto Aichel, who suggested in 1911 that a cancer cell under attack by a white blood cell might spontaneously fuse with that cell to produce a hybrid cell with chromosomal abnormalities that could lead to cancer. Aichel’s theory was largely dismissed by his contemporaries, but recent discoveries about the broader role of cell fusion in tissue homeostasis and regeneration have revived interest in his ideas. Today there is strong evidence of fusion between cancer and normal cells in human cancer, but it has not been apparent whether cell fusion events could be giving cancer cells a selective advantage and enhancing cancer progression.

As cancer progresses, tumor cells must acquire new capabilities, or phenotypes. They must start to grow in an uncontrolled manner, then be able to leave their site of origin, and then later become resistant to anti-cancer drugs. Many new cancer cell phenotypes arise from changes to the cancer genome that accumulate over time, but this new work suggests that spontaneous fusion of cancer cells with macrophages, white blood cells normally associated with defending the body, can also deliver significant new advantages to tumorigenic cells.

The OHSU researchers began by confirming that cells from various types of cancer could readily and spontaneously fuse with macrophages. Then, by intensively studying the fusion-derived cancer cells, the researchers were able to identify their new behaviors. They found that fusion-derived cancer cells exhibited enhanced adhesive strength, formed tumors more rapidly than unfused cancer cells, and flourished under conditions that dramatically inhibited growth of unfused cells.

“Overall, our findings demonstrate that spontaneous fusion of cancer cells with macrophages can profoundly and significantly impact the phenotype of tumorigenic cells, with implications for our basic understanding of cancer cell biology and the process of tumor evolution,” Silk and colleagues conclude.

Instrumentation used in this work was supported by grant number S10-RR023432 from the NIH National Center for Research Resources. Research funds came from the NIH National Cancer Institute under award numbers T32CA106195 and U54CA112970 and from the NIH National Heart Lung and Blood Institute under award number T32HL007781. Support was also provided by the NIH under award number R01CA118235 to M.H.W.